Cancer biology - Hendricks Flashcards
aetiology
apoptosis
metastasis
oncogene
tumour-supressor gene
under-researched areas
early diagnosis of cancer
cancer prevention
cancer
uncontrolled proliferation of cells
benign tumour
can be contained
doesn’t escape site of development
malignant tumour
escapes membrane
can invade surrounding tissue
can enter blood stream/lymphatic vessels.
can metastasize (spread) spread to different sites
diagnosing cancer
Stain for immunohistochemistry to confirm cancer. Stain for particular structures. Can determine what kind of cancer depending on characteristics.
Most common breast cancer is pos for 3 receptors. Use antibodies for estrogen, progesterone receptor etc. These receptors can be targeted to block their function
CT scan – identify tumours in other sites of the body. If they take tissue and do biopsy and histology and can see the tissue characteristics it can give an indication of primary site.
factors that cause cancer
- Hereditary factors
- Environmental factors:
(i) Chemicals
(ii) Infectious agents (viruses and bacteria)
(iii) Radiation
percentage of cancers caused by hereditary factors
10%
Percentage of cancers caused by environmental factors
90%
Note that although 90% of cancers stem from environmental factors, the genome still plays a role in the subsequent development of a tumour. Following exposure to specific carcinogens in the environment, the genotype and phenotype of the individual in question determines whether of not they will be susceptible to developing a particular cancer
How can chemicals cause cancer?
Several chemicals contribute to the development of cancer. These can damage DNA (directly/indirectly) If key genes are affected, this can cause cancer
Exposure to carcinogenic chemicals is responsible for most cancers worldwide. These exist in the environment in isolation, or in combination with other compounds
Provide an example of how chemicals can cause cancer
Smoking and lung cancer:
More than 90% of those who develop lung cancer are smokers.
There are molecules directly responsible for the carcinogenic activity of smoke. Furthermore, xenobiotic enzymes also impact smokers’ risk of developing lung cancer
>90% of individuals who develop lung cancer are smokers, though not all smokers develop lung cancer. Why is this so?
How can infectious agents cause cancer?
Infectious agents (viruses and bacteria) can cause cancer. There is great evidence for viruses, but less for bacteria
Provide an example of how infectious agents can cause cancer
Virus: Human papilloma virus (HPV) can induce cervical cancer. It is present in >98% of cervical cancer cases. Blocking HPV genes in vitro can lead to the loss of tumorigenic potential
Bacteria: Helicobacter pylori has a strong link to gastric cancer (causes chronic inflammation through continuous infection)
Cell cycle
The cell cycle is made up of stages in which the cell grows and rests, copies its DNA, rests to check integrity of DNA, and divides into two
Regulation of G1/S control point
The transcription factor, E2F, binds particular promoters. This causes the transcription of many genes (cyclin E, cyclin A, etc) and drives the cell from G0/G1 to S phase
E2F does not always carry out this function!
E2F is bound to a protein called RB.
Growth factor is released and activates a receptor, triggering cyclin D/CDK complex phosphorylate RB.
When RB is phosphorylated many times, it has less affinity for E2F, and releases E2F/
Phosphate is very negatively charged. Causes change in conformation of protein and gets released
Serine, threonine and tyrosine are phosphorylated (all have hydroxyl groups)
What is the role of E7 in the tumorigenesis of HPV?
Role of E7 in tumorigenesis of HPV:
E7 (oncogene) in HPV mimics the phosphorylation of RB.
It competes for the binding to E2F. E7 binds to RB, displacing E2F. E2F is released and carries out all of its usual functions.
This is how HPV helps to facilitate cervical cancer
Provides growth stimulus for these cells
Explain how gene methylation can facilitate carcinogenesis
Gene methylation as an epigenetic process that alters expression of genes, and can facilitate carcinogenesis.
on the promoter of a gene you change the methylation pattern. When this happens, you change the regualtion of that gene. A gene that is usually turned on is now turned off by methylating cpg islands.
If you have a gene, in front of the gene you have a prmotoer (sequence cpg) when methylated, u turn the gene off. If you take methyl group away, the promoter can bind the transcriptional factor and gene is activated.
There are many tumour supressor genes that are inactivated by methylated.
What is our working hypothesis of cancer development called? Define it
The somatic mutation theory
Exposure to carcinogens over time result in multiple mutational events in different genes of the same cell (or progeny of those cells)
These accumulated alterations affect enough critical homeostatic pathways to transform the cell into a cancer cell.
Explain the generally-accepted model of tumorigenesis
A cell is affected by a carcinogen, causing a mutation. This can alter certain regulatory pathways (for example, proliferation)
The daughter cells will acquire this mutation too
At another point in time, the same carcinogen, or a different one, affects one of these daughter cells (which already has a mutation) resulting in a second mutation
This process can occur a number of times. As these mutations accumulate, the cells change from normal to a tumour.
This is a multi-step, multi-gene process
Critical regulatory circuits affected by cancer
Certain genes which are altered by cancer participate in critical regulatory circuits within the cell.
Their alteration results in the dysregulation of critical homeostatic pathways
his results in the accumulation of characteristics / hallmarks associated with cancer!
Some of these circuits include:
- motility circuits
- cytostasis and differentiation circuits
- proliferation circuits
- viability circuits
In cancers, certain functional pathways seem particularly prone to alteration
